Journal
CANCER IMMUNOLOGY IMMUNOTHERAPY
Volume 57, Issue 10, Pages 1471-1481Publisher
SPRINGER
DOI: 10.1007/s00262-008-0485-6
Keywords
breast neoplasms; neoplasm metastasis; leukocytes; granulocytes; fatigue; inflammation
Categories
Funding
- NCI NIH HHS [P30 CA016058, R01 CA092704-08, P30 CA16058, R01 CA92704, P30 CA016058-339029, R01 CA092704, K05 CA098133-04, K05 CA098133] Funding Source: Medline
- NCRR NIH HHS [M01-RR0034, UL1 RR025755, M01 RR000034-476249, M01 RR000034] Funding Source: Medline
- NIMH NIH HHS [R01 MH051487, 1 R01 MH51487, R01 MH051487-05] Funding Source: Medline
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A period of tumor growth precedes the clinical detection of breast cancer recurrence. We explore immune, endocrine, and behavioral parameters during this period. We conducted a phase III clinical trial in which women with surgically treated stage II/III breast cancer (N = 227) were randomized to receive a psychological intervention or assessment-only and then regularly assessed for 10 years. Patients who recurred (R, n = 48) were matched with patients remaining disease-free (DF, n = 48) on demographic and prognostic characteristics, treatment, and duration of disease-free follow-up. Data at three assessment points, occurring, on average, 17, 11, and 4 months before the recurrence was detected clinically, with equivalent time points for the disease-free group, were examined. Mixed-effects models tested for group differences in immune cell counts and function as well as endocrine and behavioral parameters. In the 17 months prior to recurrence detection, patients exhibited higher white blood cell count, neutrophil, lymphocyte, and natural killer cell counts, relative to DF patients. R patients also showed higher cortisol, worse physical functioning, fatigue, and quality of life. Follow-up analyses showed patients with local recurrences to differ from those with distant recurrence, with the former exhibiting elevated natural killer cell cytotoxicity, lymphocyte proliferative response, fatigue, pain, and emotional distress (depression, anxiety), and the latter exhibiting higher neutrophil, lymphocyte, and natural killer cell counts. Patients who would recur showed reliable biobehavioral alterations more than a year prior to their diagnosis. This novel observation may contribute to our understanding of the disease relapse processes.
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